Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy
<p>Hypoxia induced factor (HIF) transcriptional complex is a potent inducer of cytokines that enhances therapeutic potential of stem cell. Here, ethyl 2-(2,3-dihyroxybenzamido) acetate (EDBA) was used to stabilize HIF-α in cardiosphere-derived cells (CDCs) with the aim of e...
| Main Authors: | , , , , |
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| Format: | Journal article |
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Universiti Sains Malaysia
2016
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| _version_ | 1797074224523771904 |
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| author | Schofield, C Tan, S Yeoh, K Heather, L Carr, C |
| author_facet | Schofield, C Tan, S Yeoh, K Heather, L Carr, C |
| author_sort | Schofield, C |
| collection | OXFORD |
| description | <p>Hypoxia induced factor (HIF) transcriptional complex is a potent inducer of cytokines that enhances therapeutic potential of stem cell. Here, ethyl 2-(2,3-dihyroxybenzamido) acetate (EDBA) was used to stabilize HIF-α in cardiosphere-derived cells (CDCs) with the aim of enhancing their therapeutic potential for myocardial infarction. In this study, neonatal Sprague Dawley (SD) rat hearts (n=12) were excised, minced and cultured to generate explant-derived cells (EDCs) which were subsequently expanded into monolayer cardiosphere-derived cells (CDCs). CDCs were treated with 0.5mM EDBA for 24h before RNA (n=4), protein (n=4) and culture medium (n=4) were collected for genomic, proteomic and metabolic analysis. All data were presented as mean ± standard deviation, SD. EDBA-treated CDCs showed significant increased HIF-1α mRNA expression (2.4 ± 0.6-fold, p < 0.01) after 24 hours, compared with non-treated control cells. EDBA significantly increased cardiac stem cell marker, c-Kit (1.5 ± 0.2-fold, p < 0.05) and reduced the cardiac mesenchymal cell markers, CD90 and CD105 (both 0.7 ± 0.2-fold, p < 0.05), generating a culture containing higher c-Kit+ cardiac stem cell population. EDBA treatment also significantly increased the expression of cytokines (p < 0.05) involved in stem cell trafficking (CXCR4, 5.1 ± 2.0-fold), erythropoiesis (EPO, 2.2 ± 0.7-fold) and angiogenesis (VEGF, 2.0 ± 0.6-fold), enhancing the therapeutic potential of CDCs for myocardial infarction. Of note, EDBA significantly increased glucose uptake (2.4 ± 0.2-fold, p < 0.05) and lactate accumulation (2.0 ± 0.1-fold, p < 0.01) in the CDC culture medium, suggesting increased glycolytic metabolism. Further, EDBA significantly reduced oxygen consumption in CDC by 80% (p < 0.05), suggesting that treated cells could survive better after transplantation into the hypoxic infarcted myocardium. In conclusion, EDBA stabilized HIF-1α, which induced metabolic changes in the CDCs. This work could impact on cardiac stem cell therapy for myocardial infarction.</p> |
| first_indexed | 2024-03-06T23:33:03Z |
| format | Journal article |
| id | oxford-uuid:6cb6b24a-5d5a-49b8-9f2f-54dcd095b0a9 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:33:03Z |
| publishDate | 2016 |
| publisher | Universiti Sains Malaysia |
| record_format | dspace |
| spelling | oxford-uuid:6cb6b24a-5d5a-49b8-9f2f-54dcd095b0a92022-03-26T19:12:56ZEthyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6cb6b24a-5d5a-49b8-9f2f-54dcd095b0a9Symplectic Elements at OxfordUniversiti Sains Malaysia2016Schofield, CTan, SYeoh, KHeather, LCarr, C<p>Hypoxia induced factor (HIF) transcriptional complex is a potent inducer of cytokines that enhances therapeutic potential of stem cell. Here, ethyl 2-(2,3-dihyroxybenzamido) acetate (EDBA) was used to stabilize HIF-α in cardiosphere-derived cells (CDCs) with the aim of enhancing their therapeutic potential for myocardial infarction. In this study, neonatal Sprague Dawley (SD) rat hearts (n=12) were excised, minced and cultured to generate explant-derived cells (EDCs) which were subsequently expanded into monolayer cardiosphere-derived cells (CDCs). CDCs were treated with 0.5mM EDBA for 24h before RNA (n=4), protein (n=4) and culture medium (n=4) were collected for genomic, proteomic and metabolic analysis. All data were presented as mean ± standard deviation, SD. EDBA-treated CDCs showed significant increased HIF-1α mRNA expression (2.4 ± 0.6-fold, p < 0.01) after 24 hours, compared with non-treated control cells. EDBA significantly increased cardiac stem cell marker, c-Kit (1.5 ± 0.2-fold, p < 0.05) and reduced the cardiac mesenchymal cell markers, CD90 and CD105 (both 0.7 ± 0.2-fold, p < 0.05), generating a culture containing higher c-Kit+ cardiac stem cell population. EDBA treatment also significantly increased the expression of cytokines (p < 0.05) involved in stem cell trafficking (CXCR4, 5.1 ± 2.0-fold), erythropoiesis (EPO, 2.2 ± 0.7-fold) and angiogenesis (VEGF, 2.0 ± 0.6-fold), enhancing the therapeutic potential of CDCs for myocardial infarction. Of note, EDBA significantly increased glucose uptake (2.4 ± 0.2-fold, p < 0.05) and lactate accumulation (2.0 ± 0.1-fold, p < 0.01) in the CDC culture medium, suggesting increased glycolytic metabolism. Further, EDBA significantly reduced oxygen consumption in CDC by 80% (p < 0.05), suggesting that treated cells could survive better after transplantation into the hypoxic infarcted myocardium. In conclusion, EDBA stabilized HIF-1α, which induced metabolic changes in the CDCs. This work could impact on cardiac stem cell therapy for myocardial infarction.</p> |
| spellingShingle | Schofield, C Tan, S Yeoh, K Heather, L Carr, C Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy |
| title | Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy |
| title_full | Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy |
| title_fullStr | Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy |
| title_full_unstemmed | Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy |
| title_short | Ethyl 2-(2,3-dihyroxybenzamido) ccetate induces hypoxia induced factor-related metabolic changes in cardiosphere-derived cells for myocardial infarction therapy |
| title_sort | ethyl 2 2 3 dihyroxybenzamido ccetate induces hypoxia induced factor related metabolic changes in cardiosphere derived cells for myocardial infarction therapy |
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